Background. Cardiac resynchronization therapy (CRT) is a current standard for the treatment of patients with severe CHF. A marker for beneficial response to CRT is being searched for. Aim. To evaluate time-related changes in levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and inflammation mediators in patients with different responses to CRT. Materials and methods. The study included 47 patients with CHF (78.7 % men, mean age 54.5±8.7) who were implanted with CRT devices. EchoCG was performed and levels of NT-proBNP, interleukin-6 (IL-6), С-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) were measured for all patients at baseline, 12 months and 24 months of follow-up. Patients were divided into three groups based on the time-related decrease in LV end systolic volume (ESV) following the CRT device implantation: patients with LV ESV reduced by >15 % constituted the responder group (n=29; 61.7 %); patients with LV ESV reduced from 5 to 15 % constituted the non-progressor group (n=9; 19.1 %); and patients with LV ESV reduced by <5 % constituted the non-responder group (n=9; 19.1 %). Results. In the responder group, significant decreases were observed for concentrations of NT-proBNP (р=0.039; р=0.018), IL-6 (р=0.035; р=0.028), and TNF-α (р=0.035; р=0.043) throughout the entire follow-up period. The CRP level was significantly decreased at 12 months but did not differ from baseline values at 24 months of observation (р=0.034; р=0.139). In the non-progressor group, NT-proBNP was decreasing during the first years. However at 24 months, the NT-proBNP level did not significantly differ from baseline (р=0.029; р=0.477), and changes in inflammation mediators were not observed. In the non-responder group, levels of NT-proBNP and inflammation mediators did not differ from baseline values during the entire follow-up period. Conclusion. A positive response to CRT is associated with reduced neuro-humoral activity and systemic inflammation. The neuro-humoral background decreases in the first year; however, further improvement and decreases in inflammation mediators were not observed in the remote period. Probably, the complex decrease in levels of NT-proBNP and inflammation mediators can be used as a marker for a beneficial response to CRT.